The Olson lab identifies, prioritizes, and advances therapeutics into clinical trials for children with brain cancer, with increasing focus on types of brain tumors that are uncommon and have the greatest need for translational research. We intend to increase the cure rate for children with these types of brain cancer by at least 10% due specifically to work done by our team.
In the past, much of our drug development work focused on therapeutic molecules discovered in the pharmaceutical industry. Increasingly, we are identifying new targets for cancer therapy (BUB1B and PHF5A, in collaboration with the Paddison and Bradley labs). Our team plays a leading role in a new peptide drug discovery program that has potential to identify and advance more effective and less toxic drugs for brain diseases including cancer, neurodevelopmental disorders (e.g., forms of autism), neurodegenerative disorders, mental health disorders, and brain cancer. Please see the Project Violet website for more information.
We integrate cutting edge genomics, advanced mouse models of human-derived tumors, functional genomic analyses, and a truly novel approach to advancing effective drug combinations. Our program has advanced laboratory-based research to four national clinical trials, of which Dr. Olson leads Children’s Oncology Group (COG) ACNS0332 Phase III trial for high risk medulloblastoma/primitive neuroectodermal tumor (PNET) patients. He also co-chairs development of the upcoming COG Phase III trial for standard risk medulloblastoma patients. We receive fresh surgical brain tumor tissue from COG institutions and establish cancer stem cell cultures and orthotopic patient-derived xenograft (PDX) mouse models from these. We established 24 such models last year alone and these represent tumor classes that have never been represented by a bona fide mouse model in the past – including PNETs, pineoblastoma, diffuse intrinsic brainstem glioma, ependymoma and atypical teratoid rhabdoid tumors. The cancer stem cell lines undergo functional genomics screening with RNAi that knocks down individual kinases, transcription factors, or the entire genome, depending on the project. This serves as a foundation for further synthetic lethal or drug sensitization studies that identify candidate combinations of therapies that are tailored to the molecular vulnerabilities of subsets of patients. We use the mouse models to test hypotheses generated by the screening and validation programs, with anticipation of advancing the most effective combinations of drugs into the next generation of national clinical trials through the multiple clinical trial consortia to which we belong.
Banner image one and three credited to Chris Baron